title: Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
abstract: BACKGROUND
  The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation.
  
  
  METHODS
  Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion).
  
  
  RESULTS
  Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm(3) and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively.
  
  
  CONCLUSIONS
  Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.
authors.affiliation: Medical Research Council, University College London, London, United Kingdom ; Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Lodi
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: David
authors.initials: D
authors.lastname: Hawkins
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.forename: Ken
authors.initials: K
authors.lastname: McLean
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Frank
authors.initials: F
authors.lastname: Post
authors.forename: Anne M
authors.initials: AM
authors.lastname: Johnson
authors.forename: Louise
authors.initials: L
authors.lastname: Walker-Nthenda
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
mesh_terms: D019380:Anti-HIV Agents / Q000276:immunology / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000276:immunology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D024882:Drug Resistance, Viral / Q000276:immunology*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006678:HIV / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008297:Male; D012306:Risk; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents